title: Structural basis for the interaction between carbonic anhydrase and 1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamides.
abstract: Isoquinolinesulfonamides inhibit human carbonic anhydrases (hCAs) and display selectivity toward therapeutically relevant isozymes. The crystal structure of hCA II in complex with 6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-2-ylsulfonamide revealed unusual inhibitor binding. Structural analyses allowed for discerning the fine details of the inhibitor binding mode to the active site, thus providing clues for the future design of even more selective inhibitors for druggable isoforms such as the cancer associated hCA IX and neuronal hCA VII.
authors.affiliation: Department of Structural Biology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Mader
authors.forename: Jiří
authors.initials: J
authors.lastname: Brynda
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Stefano
authors.initials: S
authors.lastname: Agnello
authors.forename: Petr
authors.initials: P
authors.lastname: Pachl
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
authors.forename: Pavlína
authors.initials: P
authors.lastname: Řezáčová
mesh_terms: D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D007546:Isoquinolines; D024402:Carbonic Anhydrase II